WO2002016304A1 - Procede de production d'esters de dialkyle d'acide alpha-fluoromalonique - Google Patents

Procede de production d'esters de dialkyle d'acide alpha-fluoromalonique Download PDF

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Publication number
WO2002016304A1
WO2002016304A1 PCT/EP2001/009320 EP0109320W WO0216304A1 WO 2002016304 A1 WO2002016304 A1 WO 2002016304A1 EP 0109320 W EP0109320 W EP 0109320W WO 0216304 A1 WO0216304 A1 WO 0216304A1
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WO
WIPO (PCT)
Prior art keywords
trialkylamine
hydrogen fluoride
compounds
general formula
hours
Prior art date
Application number
PCT/EP2001/009320
Other languages
German (de)
English (en)
Inventor
Thorsten Müh
Paul Fiedler
Holger Weintritt
Winfried Westerkamp
Arndt Reinecke
Original Assignee
Bayer Cropscience Ag
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bayer Cropscience Ag filed Critical Bayer Cropscience Ag
Priority to AU2001289799A priority Critical patent/AU2001289799A1/en
Publication of WO2002016304A1 publication Critical patent/WO2002016304A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/307—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of halogen; by substitution of halogen atoms by other halogen atoms

Definitions

  • the invention relates to a new, advantageous process for the preparation of ⁇ -fluoro-malonic acid dialkyl esters.
  • ⁇ -Fluoro-malonic acid dialkyl esters are intermediates which can be used, for example, for the production of ⁇ -fluoro-acrylic acid esters (cf. EP-A-203 462).
  • ⁇ -fluoro-acrylic acid esters high-molecular, non-crystalline polymers are produced that are transparent and have softening temperatures above 10 ° C.
  • ⁇ -fluoro- ⁇ -keto ester can be obtained starting from ethyl bromofluoroacetate.
  • ethyl bromofluoroacetate is reacted in a first reaction step with tri-n-butylphoshin to give the corresponding phosphonium salt, which is then converted into the corresponding ylene by reaction with n-butyllithium at -78 ° C.
  • ⁇ -fluoro- ⁇ -keto esters are obtained (cf. J. Org. Chem. 56, 273-277 (1991)).
  • a major disadvantage of this process is the difficult accessibility of the starting products, the multi-stage process and the necessary complex procedure e.g. when handling phosphines and n-butyllithium, which require special safety measures and carry out the reaction at low temperatures. For this reason, this method cannot be used on an industrial scale.
  • ⁇ -fluoro- ⁇ -dicarbonyl compounds of the formula (B) are prepared starting from dicarbonyl compounds of the formula (A) by reaction with an adduct of hydrogen fluoride Trialkylamine at temperatures from 20 ° C to 100 ° C.
  • the disadvantage of this process is the long reaction times, which are between 24 hours and 72 hours. Another disadvantage is that the product is only obtained in yields of 60% to 70%.
  • R 1 represents alkoxy having 1 to 6 carbon atoms
  • R 2 represents hydrogen or fluorine
  • R 3 represents hydrogen, fluorine or chlorine
  • R 1 is in particular methoxy or ethoxy.
  • R 1 particularly preferably represents ethoxy.
  • R is in particular hydrogen.
  • the method according to the invention has a number of advantages.
  • ⁇ -fluoro-malonic acid dialkyl esters are obtained after half the reaction time, which is customary in known processes.
  • the reaction time is 12 hours, while in known processes it takes 24 to 72 hours to react (cf. DE-A 42 37 892).
  • Another advantage is that the yields are at least 15% higher than conventional processes. The new process is therefore particularly well suited for large-scale use.
  • the dicarbonyl compounds of the general formula (II) and all other starting compounds are common commercial products or can be prepared from them by simple processes.
  • addition products of hydrogen fluoride onto trialkylamines are generally used which contain 1 to 3 moles of hydrogen fluoride per mole of trialkylamine, and this is preferably located
  • trialkylamines examples include those which contain the same or different alkyl groups each having 1 to 6 carbon atoms. Trialkylamines with three identical alkyl groups are preferred. Triethyl-a in is particularly preferred.
  • the addition products of hydrogen fluoride onto trialkylamine can be prepared in situ by metering triethylamine into liquid hydrogen fluoride.
  • the addition products of hydrogen fluoride on trialkylamine can be obtained in situ by metering hydrogen fluoride into triethylamine.
  • reaction temperatures can be varied within a substantial range when carrying out the process according to the invention.
  • temperatures from 103 ° C to 130 ° C, preferably at temperatures from 104 ° C to 110 ° C, particularly preferably at temperatures from 104 ° C to 107 ° C.
  • the process according to the invention is generally carried out under increased pressure (autogenous pressure). Generally one works at pressures of 1.3 to 9 bar, preferably at pressures of 1.3 to 4 bar.
  • 1 to 4 moles of the adduct preferably 1 per mole of the compounds of the formula (II) are generally employed per mole of the compounds of the formula (II) 3 moles a.
  • the procedure according to the invention is generally carried out as follows: The addition product of hydrogen fluoride onto trialkylamine is placed in a pressure-tight reaction vessel. The reaction vessel is closed pressure-tight and the reaction mixture heated to 103 ° C to 130 ° C. The dicarbonyl compounds of the general formula (II) are metered into this. The reaction mixture obtained is stirred after the addition. A pressure of 1.3 to 9 bar is established. It is then cooled, the reaction mixture is let down and water is added. The organic phase is separated off, washed with acid and optionally distilled.
  • the metering time of the dicarbonyl compounds of the general formula (II) is generally three to nine hours, in particular five to seven hours, particularly preferably 6 hours.
  • reaction mixture is generally stirred for a further three to nine hours, in particular five to seven hours, particularly preferably a further six hours.
  • the process according to the invention is used, for example, for the preparation of dimethyl ⁇ -fluoromalonic acid, which is used, for example, as an intermediate for
  • ⁇ -fluoro-acrylic acid esters (cf. EP-A-203 462) can be used.
  • ⁇ -fluoro-acrylic acid esters high-molecular, non-crystalline polymers are produced that are transparent and have softening temperatures above 10 ° C.
  • ⁇ -fluoro-malonic acid diethyl ester can be used for the preparation of fluorine-substituted heterocycles, for example are biologically active or of interest as intermediates for crop protection agents (cf. N. Ishikawa, J. Fluorine Chem. 1984, 25, 203, or EP-A 970057).
  • Diethyl chloromalonate (purity 77%; 1 mol) is metered in at 105 ° C. using a pump. After the addition has ended, the reaction mixture is stirred at 105 ° C. for a further 6 hours. It is then cooled to 40 ° C., the reaction vessel is depressurized and 600 g of water are added. The organic phase is washed with 100 g of 15% sulfuric acid. 223 g of a dark liquid, 74%

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'invention concerne un nouveau procédé avantageux permettant de produire des esters de dialkyle d'acide alpha-fluoromalonique de formule générale (I) en faisant réagir un composé de formule générale (II) avec un produit provenant de l'addition de fluor-hydrogène et d'un trialkylamine, sous pression et à des températures de 103 °C à 130 °C. Dans les formules (I) et (II), R1 désigne alcoxy C¿1?-C6, R?2¿ désigne hydrogène ou fluor et R3 désigne hydrogène, fluor ou chlore.
PCT/EP2001/009320 2000-08-24 2001-08-13 Procede de production d'esters de dialkyle d'acide alpha-fluoromalonique WO2002016304A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2001289799A AU2001289799A1 (en) 2000-08-24 2001-08-13 Method for producing alpha fluoromalonic acid dialkyl esters

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE2000141618 DE10041618A1 (de) 2000-08-24 2000-08-24 Verfahren zur Herstellung von alpha-Fluor-malonsäuredialkylestern
DE10041618.7 2000-08-24

Publications (1)

Publication Number Publication Date
WO2002016304A1 true WO2002016304A1 (fr) 2002-02-28

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2001/009320 WO2002016304A1 (fr) 2000-08-24 2001-08-13 Procede de production d'esters de dialkyle d'acide alpha-fluoromalonique

Country Status (3)

Country Link
AU (1) AU2001289799A1 (fr)
DE (1) DE10041618A1 (fr)
WO (1) WO2002016304A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007502793A (ja) * 2003-08-18 2007-02-15 バイエル・クロツプサイエンス・アクチエンゲゼルシヤフト α−フルオロマロン酸ジアルキルエステルの製造方法
CN109824512A (zh) * 2019-02-26 2019-05-31 国药集团化学试剂有限公司 一种2-氟丙二酸二甲酯的制备方法

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10203044A1 (de) * 2002-01-26 2003-07-31 Solvay Fluor & Derivate Extraktionsverfahren

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4237882A1 (de) * 1992-11-10 1994-05-11 Bayer Ag Verfahren zur Herstellung von alpha-Fluor-beta-dicarbonylverbindungen

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4237882A1 (de) * 1992-11-10 1994-05-11 Bayer Ag Verfahren zur Herstellung von alpha-Fluor-beta-dicarbonylverbindungen
EP0597329A2 (fr) * 1992-11-10 1994-05-18 Bayer Ag Procédé de préparation de composés alpha-fluorés-bêta-dicarbonylés

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DATABASE CROSSFIRE BEILSTEIN Beilstein Institut zur Förderung der Chemischen Wissenschaften, Frankfurt am Main, DE; XP002186926 *

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007502793A (ja) * 2003-08-18 2007-02-15 バイエル・クロツプサイエンス・アクチエンゲゼルシヤフト α−フルオロマロン酸ジアルキルエステルの製造方法
US7807851B2 (en) 2003-08-18 2010-10-05 Bayer Cropscience Ag Method for producing α-fluoromalonic acid dialkyl esters
CN1894198B (zh) * 2003-08-18 2012-07-18 拜尔农作物科学股份公司 生产α-氟代丙二酸二烷基酯的方法
KR101167233B1 (ko) * 2003-08-18 2012-07-23 바이엘 크롭사이언스 아게 α-플루오로말론산 디알킬 에스테르의 제조방법
JP2013241421A (ja) * 2003-08-18 2013-12-05 Bayer Cropscience Ag α−フルオロマロン酸ジアルキルエステルの製造方法
JP2014139174A (ja) * 2003-08-18 2014-07-31 Bayer Cropscience Ag α−フルオロマロン酸ジアルキルエステルの製造方法
CN109824512A (zh) * 2019-02-26 2019-05-31 国药集团化学试剂有限公司 一种2-氟丙二酸二甲酯的制备方法
CN109824512B (zh) * 2019-02-26 2021-06-08 国药集团化学试剂有限公司 一种2-氟丙二酸二甲酯的制备方法

Also Published As

Publication number Publication date
DE10041618A1 (de) 2002-03-07
AU2001289799A1 (en) 2002-03-04

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